CYP2D6 ultrarapid metabolizer genotype as a potential modifier of smoking behaviour

Citation
St. Saarikoski et al., CYP2D6 ultrarapid metabolizer genotype as a potential modifier of smoking behaviour, PHARMACOGEN, 10(1), 2000, pp. 5-10
Citations number
31
Categorie Soggetti
Pharmacology & Toxicology
Journal title
PHARMACOGENETICS
ISSN journal
0960314X → ACNP
Volume
10
Issue
1
Year of publication
2000
Pages
5 - 10
Database
ISI
SICI code
0960-314X(200002)10:1<5:CUMGAA>2.0.ZU;2-7
Abstract
Some 3-10% of Caucasians are deficient in CYP2D6 metabolism (poor metaboliz ers), due to inheritance of two defective alleles, whereas amplification of the CYP2D6 gene results in ultrarapid metabolism in 1-2% of Caucasian popu lations, To examine the possible association between CYP2D6 polymorphism an d individual smoking behaviour, we analysed the prevalence of CYP2D6 genoty pes among 292 long-term heavy smokers, 382 individuals with more variable s moking histories, and 302 never-smokers. The prevalence of ultrarapid metab olizers in heavy smokers (7.9%) was twofold compared to individuals with va riable smoking habits (3.7%; odds ratio 2.3, 95% confidence interval 1.2-4. 4), and fourfold compared with never-smokers (2.0%) (odds ratio 4.2, 95% co nfidence interval 1.8-9.8), The frequency of poor metabolizer genotype was approximately 2%, in each smoker group. However, when men and women were st udied separately, the prevalence of poor metabolizer genotype was higher in male never-smokers (3.6%) than in variable smokers (2.7%) and heavy smoker s (2.2%), Moreover, a trend test, adjusted by age, gender and cancer status , revealed a significant trend for the increased tobacco usage with increas ed metabolic capacity, Our results are in agreement with the assumption tha t increased CYP2D6 activity may contribute to the probability of being addi cted to smoking. Pharmacogenetics 10:5-10 (C) 2000 Lippincott Williams & Wi lliams.